By means of newly constructed receptor assays for insulin and growth hormone, we wish to extend and develop new investigations in four major areas. Specifically, we intend, first, to define the absence of receptor defects for growth hormone in proportional dwarfs possessing growth hormone. Receptor activity of endogenous growth hormone produced by these individuals will be investigated. In the complex field of the metabolism of starvation, we will investigate the interrelationship of substrates mobilized in fasting with tissue receptors for growth hormone and insulin. Such studies on the growth hormone and insulin receptors will include dose response data for betahydroxybutyrate, acetoacetate, and free fatty acids - studied separately and in combination. This will provide information on the part played by these substances in altering "tissue receptivity" in fasting and in diabetic ketoacidosis. Our preliminary data will be given in this proposal. During a ten year follow up of 48 patients with an isolated deficiency of growth hormone, the interaction and relative importance of three variables on the glucuronic pathway will be examined. This pathway is essential for "diversion" of glucose to pathways leading to synthesis of glycoprotein and mucopolysaccharides- both of which may be quantitatively and qualitatively abnormal in the diabetic.